Effects of a specific cysteinyl leukotriene antagonist, pranlukast, on antigen-induced cysteinyl leukotriene-mediated rhinitis in guinea pigs.
To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclooxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas thromboxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1-10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indomethacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.
Fujita
M
M
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Mishima-gun, Osaka, Japan.
Yonetomi
Y
Y
Takeda
H
H
Nakagawa
N
N
Kawabata
K
K
Ohno
H
H
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010047:Ovalbumin; D010793:Phthalazines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000188:drug therapy*; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000378:metabolism
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D006634:Histamine H1 Antagonists; D020024:Leukotriene Antagonists; D010793:Phthalazines; D013189:SRS-A; D013929:Thromboxane B2; D010047:Ovalbumin; D011738:Pyrilamine; C047681:pranlukast; D007213:Indomethacin; C020976:azelastine